Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000698231 | SCV000826883 | pathogenic | Developmental and epileptic encephalopathy, 9 | 2020-01-04 | criteria provided, single submitter | clinical testing | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PCDH19 protein function. For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with clinical features of PCDH19-related epilepsy (PMID: 22946748,21053371, 27179713). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with arginine at codon 81 of the PCDH19 protein (p.Leu81Arg). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and arginine. |